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The causative agent of severe fever with thrombocytopenia syndrome (SFTS) is Bandavirus dabieense, an emerging tick-borne zoonotic pathogen. Migratory birds have often been suggested as potential carriers of ticks that can transmit Bandavirus dabieense; however, their role remains unclear. The Republic of Korea (ROK) holds an important position as a stopover on the East Asian-Australasian Flyway. The present study aimed to investigate the potential involvement of migratory birds in the transmission of the SFTS virus (SFTSV) in the ROK. A total of 4,497 ticks were collected across various regions, including Heuksando and Daecheongdo, in the ROK, from bird migration seasons in 2022 and 2023. Genetic analysis of the SFTSV was performed for 96 ticks collected from 20 different species of migratory birds. Polymerase chain reaction (PCR) fragments of SFTSV were detected in one Haemaphysalis concinna nymph collected from a Black-faced Bunting (Emberiza spodocephala) and one Ixodes turdus nymph collected from an Olive-backed Pipit (Anthus hodgsoni) on Daecheongdo and Heuksando, respectively, during their northward migration in two spring seasons. This finding suggests that migratory birds can be considered as possible carriers and long-distance dispersers of ticks and associated tick-borne diseases. This study highlights the importance of clarifying the role and impact of migratory birds in the rapid expansion of tick-borne diseases, facilitating enhanced preparedness and the development of mitigation measures against emerging SFTS across and beyond East Asia., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

α-In 2 Se 3 semiconductor crystals realize artificial synapses by tuning in-plane and out-of-plane ferroelectricity with diverse avenues of electrical and optical pulses. While the electrically induced ferroelectricity of α-In 2 Se 3 shows synaptic memory operation, the optically assisted synaptic plasticity in α-In 2 Se 3 has also been preferred for polarization flipping enhancement. Here, the synaptic memory behavior of α-In 2 Se 3 is demonstrated by applying electrical gate voltages under white light. As a result, the induced internal electric field is identified at a polarization flipped conductance channel in α-In 2 Se 3 /hexagonal boron nitride (hBN) heterostructure ferroelectric field effect transistors (FeFETs) under white light and discuss the contribution of this built-in electric field on synapse characterization. The biased dipoles in α-In 2 Se 3 toward potentiation polarization direction by an enhanced internal built-in electric field under illumination of white light lead to improvement of linearity for long-term depression curves with proper electric spikes. Consequently, upon applying appropriate electric spikes to α-In 2 Se 3 /hBN FeFETs with illuminating white light, the recognition accuracy values significantly through the artificial learning simulation is elevated for discriminating hand-written digit number images., (© 2024 Wiley‐VCH GmbH.)

Tick-borne diseases have a significant impact on human and animal populations, posing an increasing threat to public health, particularly in the context of climate change. Along with the various natural hosts of ticks, birds play a notable role in transmitting ticks and tick-borne pathogens, indicating the importance of monitoring flyways and establishing a cooperative network for comprehensive surveillance and to collect diverse tick samples across various regions. This study aimed to develop an international network for surveillance of disease, collection of sufficient tick samples, and overall identification of the geographical distribution of host and ticks in Asian regions, especially in 11 countries on East Asian and Central Asian flyways. Ticks were collected from wild animals, domestic animals, and vegetation to identify the differences between Ixodid ticks and understand tick distribution. We collected a total 6,624 of ticks from 11 collaborating Asian countries, the Republic of Korea (ROK), Japan, Thailand, Philippines, Indonesia, Cambodia, Vietnam, Taiwan, Hong Kong, Mongolia and Pakistan. We identified 17 host animals and 47 species of both residential and migratory birds. Ticks from birds collected from four countries (ROK, Japan, Hong Kong and Mongolia) belonged to two genera, Haemaphysalis and Ixodes, including Haemaphysalis (H.) longicornis, H. flava, H. concinna, H. hystricis, H. formosensis, Ixodes (I.) nipponensis and I. persulcatus. The potential of migratory birds to cross ecological barriers with ticks and tick-borne diseases indicated the need for further investigations to understand the migration of birds as potential vectors and the new influx of zoonotic diseases along migratory bird flyways. This study suggests the potential risk of spreading tick-borne diseases through birds, thus highlighting the importance of international cooperative networking., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

A new copper indium selenide, Ba 3.5 Cu 7.55 In 1.15 Se 9 , was synthesized by the KBr flux reaction at 800 °C. The compound crystallizes with orthorhombic Pnma , a = 46.1700(12) Å, b = 4.26710(10) Å, c = 19.8125(5) Å, and Z = 8. The structural framework mainly consists of four sites of cubane-type defective M 4 Se 3 (M = Cu, Cu/In) units with disordered Cu + /In 3+ ions present at the part corner of each unit. The single crystal emits intense photoluminescence at 657 nm with a relative quantum yield (RQY) 0.2 times that of rhodamine 6G powder. The compound belongs to a direct band gap at 1.91 eV, analyzed by Tauc's plot, and the energy is close to the PL position. The Hall effect measurement on a pressed pellet reveals an n-type conductivity with a carrier concentration of 3.358 × 10 17 cm -3 and a mobility of 24.331 cm 2 V -1 s -1 . Furthermore, the compound produces a strong nonlinear third-harmonic generation (THG), with an χ S (3) value of 1.3 × 10 5 pm 2 /V 2 comparable to 1.6 × 10 5 pm 2 /V 2 for AgGaSe 2 measured at 800 nm.

In this work, we develop a gate-tunable gas sensor based on a MoS 2 /hBN heterostructure field effect transistor. Through experimental measurements and numerical simulations, we systematically reveal a principle that relates the concentration of the target gas and sensing signals (Δ I / I 0 ) as a function of gate bias. Because a linear relationship between Δ I / I 0 and the gas concentration guarantees reliable sensor operation, the optimal gate bias condition for linearity was investigated. Taking NO 2 and NH 3 as target molecules, it is clarified that the bias condition greatly depends on the electron accepting/donating nature of the gas. The effects of the bandgap and polarity of the transition metal dichalcogenides (TMDC) channel are also discussed. In order to achieve linearly increasing signals that are stable with respect to the gas concentration, a sufficiently large V BG within V BG > 0 is required. We expect this work will shed light on a way to precisely design reliable semiconducting gas sensors based on the characteristics of TMDC and target gas molecules.

The mixed cation compounds Na 1- x K x AsSe 2 ( x = 0.8, 0.65, 0.5) and Na 0.1 K 0.9 AsS 2 crystallize in the polar noncentrosymmetric space group Cc . The A As Q 2 ( A = alkali metals, Q = S, Se) family features one-dimensional (1D) 1 / ∞ [ AQ 2 - ] chains comprising corner-sharing pyramidal AQ 3 units in which the packing of these chains is dependent on the alkali metals. The parallel 1 / ∞ [ AQ 2 - ] chains interact via short As···Se contacts, which increase in length when the fraction of K atoms is increased. The increase in the As···Se interchain distance increases the band gap from 1.75 eV in γ-NaAsSe 2 to 2.01 eV in Na 0.35 K 0.65 AsSe 2 , 2.07 eV in Na 0.2 K 0.8 AsSe 2 , and 2.18 eV in Na 0.1 K 0.9 AsS 2 . The Na 1- x K x AsSe 2 ( x = 0.8, 0.65) compounds melt congruently at approximately 316 °C. Wavelength-dependent second harmonic generation (SHG) measurements on powder samples of Na 1- x K x AsSe 2 ( x = 0.8, 0.65, 0.5) and Na 0.1 K 0.9 AsS 2 suggest that Na 0.2 K 0.8 AsSe 2 and Na 0.1 K 0.9 AsS 2 have the highest SHG response and exhibit significantly higher laser-induced damage thresholds (LIDTs). Theoretical SHG calculations on Na 0.5 K 0.5 AsSe 2 confirm its SHG response with the highest value of d 33 = 22.5 pm/V (χ 333 (2) = 45.0 pm/V). The effective nonlinearity for a randomly oriented powder is calculated to be d eff = 18.9 pm/V (χ eff (2) = 37.8 pm/V), which is consistent with the experimentally obtained value of d eff = 16.5 pm/V (χ eff (2) = 33.0 pm/V). Three-photon absorption is the dominant mechanism for the optical breakdown of the compounds under intense excitation at 1580 nm, with Na 0.2 K 0.8 AsSe 2 exhibiting the highest stability.

Cerebral ischemia is a devastating disease that affects many people worldwide every year. The neurodegenerative damage as a consequence of oxygen and energy deprivation, to date, has no known effective treatment. The ischemic insult is followed by an inflammatory response that involves a complex interaction between inflammatory cells and molecules which play a role in the progression towards cell death. However, there is presently a matter of controversy over whether inflammation could either be involved in brain damage or be a necessary part of brain repair. The inflammatory response is triggered by inflammasomes, key multiprotein complexes that promote secretion of pro-inflammatory cytokines. An early event in post-ischemic brain tissue is the release of certain molecules and reactive oxygen species (ROS) from injured neurons which induce the expression of the nuclear factor-kappaB (NF-κB), a transcription factor involved in the activation of the inflammasome. There are conflicting observations related to the role of NF-κB. While some observe that NF-κB plays a damaging role, others suggest it to be neuroprotective in the context of cerebral ischemia, indicating the need for additional investigation. Here we discuss the dual role of the major inflammatory signaling pathways and provide a review of the latest research aiming to clarify the relationship between NF-κB mediated inflammation and neuronal death in cerebral ischemia., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Jover-Mengual, Hwang, Byun, Court-Vazquez, Centeno, Burguete and Zukin.)

APbBr 3 (A = Cs, CH 3 NH 3 ) are prototype halide perovskites having bandgaps of 2.30-2.35 eV at room temperature, rendering their apparent color nearly identical (bright orange but opaque). Upon optical excitation, they emit bright photoluminescence (PL) arising from carrier recombination whose spectral features are also similar. At 10 K, however, the apparent color of CsPbBr 3 becomes transparent yellow, whereas that of CH 3 NH 3 PbBr 3 does not change significantly due to the presence of an indirect Rashba gap. With increasing the excitation level, evolution of the PL spectra, which are excitonic at 10 K, reveals the emergence of P-band emission arising from inelastic exciton-exciton scattering. Based on the spectral location of the P-band, exciton binding energies are determined to be 21.6 ± 2.0 and 38.3 ± 3.0 meV for CsPbBr 3 and CH 3 NH 3 PbBr 3 , respectively. Intriguingly, upon further increase in the exciton density, electron-hole plasma appears in CsPbBr 3 as evidenced by both red-shift and broadening of the PL. This phase, however, does not occur in CH 3 NH 3 PbBr 3 presumably due to polaronic effects. Although the A-site cation is believed not to directly impact optical properties of APbBr 3 , our results underscore its critical role, which destines different high-density phases and apparent color at low temperatures.

Recently, halide perovskites have gained significant attention from the perspective of efficient spintronics owing to the Rashba effect. This effect occurs as a consequence of strong spin-orbit coupling under a noncentrosymmetric environment, which can be dynamic and/or static. However, there exist intense debates on the origin of broken inversion symmetry since the halide perovskites typically crystallize into a centrosymmetric structure. In order to clarify the issue, we examine both dynamic and static effects in the all-inorganic CsPbBr 3 and organic-inorganic CH 3 NH 3 PbBr 3 (MAPbBr 3 ) perovskite single crystals by employing temperature- and polarization-dependent photoluminescence excitation spectroscopy. The perovskite single crystals manifest the dynamic effect by photon recycling in the indirect Rashba gap, causing dual peaks in the photoluminescence. However, the effect vanishes in CsPbBr 3 at low temperatures (<50 K) accompanied by a striking color change of the crystal, arising presumably from lower degrees of freedom for inversion symmetry breaking associated with the thermal motion of the spherical Cs cation compared with the polar MA cation in MAPbBr 3 . We also show that the static Rashba effect occurs only in MAPbBr 3 below 90 K, presumably due to surface reconstruction via MA-cation ordering, which likely extends across a few layers from the crystal surface to the interior. We further demonstrate that this static Rashba effect can be completely suppressed upon surface treatment with polymethyl methacrylate (PMMA) coating. We believe that our results provide a rationale for the Rashba effects in halide perovskites.

Eighteen new quaternary chalcogenides A Ga M ' Q 4 ( A + = K + , Rb + , Cs + , Tl + ; M ' 4+ = Ge 4+ , Sn 4+ ; Q 2- = S 2- , Se 2- ) have been prepared by solid-state syntheses and structurally characterized using single-crystal X-ray diffraction techniques. These new phases crystallize in a variety of layered structure types. The tin analogues also adopt an extended three-dimensional network structure as polymorphs. The polymorphism and phase-stability in these cases were studied by thermal analysis and high-temperature in situ X-ray powder diffraction. All compounds are semiconductors with the colored selenides absorbing light in the infrared-green region (1.8 eV < E g < 2.3 eV) and the mostly white sulfides absorbing light in the blue-ultraviolet range (2.5 eV < E g < 3.6 eV). Based on third-harmonic generation (THG) measurements, the third-order nonlinear optical (NLO) susceptibilities χ (3) of the new and previously reported A Ga M ' Q 4 compounds were determined. These measurements revealed an apparent correlation between the THG response of the sample and its band gap, rather than the crystal structure type. While low-gap materials possess higher nonlinearity in general, we found that layered orthorhombic RbGaGeS 4 exhibits an impressive χ (3) value (about four times larger than that of AgGaS 2 ) even with a large band gap and shows stability under ambient conditions with no significant irradiation damage.

Background: It is unclear how high fructose consumption induces disparate metabolic responses in genetically diverse mouse strains., Objective: We aimed to investigate whether the gut microbiota contributes to differential metabolic responses to fructose., Methods: Eight-week-old male C57BL/6J (B6), DBA/2J (DBA), and FVB/NJ (FVB) mice were given 8% fructose solution or regular water (control) for 12 wk. The gut microbiota composition in cecum and feces was analyzed using 16S ribosomal DNA sequencing, and permutational multivariate ANOVA (PERMANOVA) was used to compare community across mouse strains, treatments, and time points. Microbiota abundance was correlated with metabolic phenotypes and host gene expression in hypothalamus, liver, and adipose tissues using Biweight midcorrelation. To test the causal role of the gut microbiota in determining fructose response, we conducted fecal transplants from B6 to DBA mice and vice versa for 4 wk, as well as gavaged antibiotic-treated DBA mice with Akkermansia for 9 wk, accompanied with or without fructose treatment., Results: Compared with B6 and FVB, DBA mice had significantly higher Firmicutes to Bacteroidetes ratio and lower baseline abundance of Akkermansia and S24-7 (P < 0.05), accompanied by metabolic dysregulation after fructose consumption. Fructose altered specific microbial taxa in individual mouse strains, such as a 7.27-fold increase in Akkermansia in B6 and 0.374-fold change in Rikenellaceae in DBA (false discovery rate <5%), which demonstrated strain-specific correlations with host metabolic and transcriptomic phenotypes. Fecal transplant experiments indicated that B6 microbes conferred resistance to fructose-induced weight gain in DBA mice (F = 43.1, P < 0.001), and Akkermansia colonization abrogated the fructose-induced weight gain (F = 17.8, P < 0.001) and glycemic dysfunctions (F = 11.8, P = 0.004) in DBA mice., Conclusions: Our findings support that differential microbiota composition between mouse strains is partially responsible for host metabolic sensitivity to fructose, and that Akkermansia is a key bacterium that confers resistance to fructose-induced metabolic dysregulation., (Copyright © The Author(s) on behalf of the American Society for Nutrition 2020.)

Understanding how individuals react differently to the same treatment is a major concern in precision medicine. Metabolic challenges such as the one posed by high fructose intake are important determinants of disease mechanisms. We embarked on studies to determine how fructose affects differential metabolic dysfunctions across genetically dissimilar mice, namely, C57BL/6 J (B6), DBA/2 J (DBA) and FVB/NJ (FVB), by integrating physiological and gene regulatory mechanisms. We report that fructose has strain-specific effects, involving tissue-specific gene regulatory cascades in hypothalamus, liver, and white adipose tissues. DBA mice showed the largest numbers of genes associated with adiposity, congruent with their highest susceptibility to adiposity gain and glucose intolerance across the three tissues. In contrast, B6 and FVB mainly exhibited cholesterol phenotypes, accompanying the largest number of adipose genes correlating with total cholesterol in B6, and liver genes correlating with LDL in FVB mice. Tissue-specific network modeling predicted strain-and tissue-specific regulators such as Fgf21 (DBA) and Lss (B6), which were subsequently validated in primary hepatocytes. Strain-specific fructose-responsive genes revealed susceptibility for human diseases such that genes in liver and adipose tissue in DBA showed strong enrichment for human type 2 diabetes and obesity traits. Liver and adipose genes in FVB were mostly related to lipid traits, and liver and adipose genes in B6 showed relevance to most cardiometabolic traits tested. Our results show that fructose induces gene regulatory pathways that are tissue specific and dependent on the genetic make-up, which may underlie interindividual variability in cardiometabolic responses to high fructose consumption., (Copyright © 2019 Elsevier B.V. All rights reserved.)

We demonstrated an effective poly(p-chloro-xylylene) (Parylene-C) encapsulation method for MAPbI 3 solar cells. By structural and optical analysis, we confirmed that Parylene-C efficiently slowed the decomposition reaction in MAPbI 3 . From a water permeability test with different encapsulating materials, we found that Parylene-C-coated MAPbI 3 perovskite was successfully passivated from reaction with water, owing to the hydrophobic behavior of Parylene-C. As a result, the Parylene-C-coated MAPbI 3 solar cells showed better device stability than uncoated cells, virtually maintaining the initial power conversion efficiency value (15.5 ± 0.3%) for 196 h.

In this study, we have fabricated hafnium oxide dielectrics for low-voltage organic and amorphous oxide thin-film transistors (TFTs) via a facile low-temperature solution method and investigated the electrical properties of these dielectrics. Hafnium oxide dielectric films can be easily fabricated by a sol-gel solution method and ultraviolet (UV) curing at room temperature. In addition, the surface energy of hafnium oxide films can be easily modified by using phosphonic-acid-based self-assembled monolayers. This modification makes these films compatible with organic semiconductors fabrication methods. These novel dielectrics exhibit excellent insulating properties (leakage current densities of <10 -6 A/cm² at 2 V), high capacitances (up to 690 nF/cm²), and smooth surfaces (root-mean-square roughness <0.5 nm). Consequently, hafnium oxide-based dielectrics can be integrated into both pentacene-based and indium oxide-based TFTs, functioning at relatively low voltages (<±3 V) to achieve good performance (hole mobility: 0.31 cm²/V · s, electron mobility: 1.54 cm²/V · s, and on/off current ratios: >10 5 ).

We synthesized multiple-cation Rb(MAFA)PbI 3 perovskite single crystals for the first time. The effect of Rb + substitution was systemically investigated, and the addition of 1.5 M 5% RbI was the optimum condition to obtain high-quality Rb(MAFA)PbI 3 single crystals. Lattice shrinkage occurred in the Rb(MAFA)PbI 3 single crystal because of the small ionic radius of Rb + , resulting in blue-shifted absorption and photoluminescence (PL) peaks. The 1.5 M 5% RbI-added (MAFA)PbI 3 single crystal showed the longest carrier lifetime of 18.35 ns, exhibiting the highest photoresponse than other crystals. We believe that this work will provide a basic insight into the mixed-cation perovskite single crystals for the future optoelectronic applications.

Purpose: Transient global ischemia arising in human due to cardiac arrest causes selective, delayed neuronal death in hippocampal CA1 and cognitive impairment. Growth arrest and DNA-damage-inducible protein 45 beta (Gadd45b) is a wellknown molecule in both DNA damage-related pathogenesis and therapies. Emerging evidence suggests that Gadd45b is an anti-apoptotic factor in nonneuronal cells and is an intrinsic neuroprotective molecule in neurons. However, the mechanism of Gadd45b pathway is not fully examined in neurodegeneration associated with global ischemia., Methods: Rats were subjected to transient global ischemia by the 4-vessel occlusion or sham operation. The animals were sacrificed at 24 hours, 48 hours, and 7 days after ischemia. The hippocampal CA1 was microdissected and processed to examine mRNA and protein level. To assess neuronal death, tissue sections were cut and processed for Fluoro-Jade and Nissl staining., Results: Here we show that ischemic insults increase abundance of Gadd45b and brain-derived neurotrophic factor, a known target of Gadd45 mediated demethylation, in selectively-vulnerable hippocampal CA1 neurons. We further show that knockdown of Gadd45b increases abundance of a pro-apoptotic Bcl-2 family member Bax while decreasing the antiapoptotic protein Bcl-2, which together promote neuronal death., Conclusion: These findings document a protective role of Gadd45b against neuronal insults associated with global ischemia and identify Gadd45b as a potential therapeutic target for the amelioration of hippocampal neurodegeneration.

Dietary fructose is a major contributor to the epidemic of diabetes and obesity, and it is an excellent model to study metabolic syndrome. Based on previous studies that Bgn gene occupies a central position in a network of genes in the brain in response to fructose consumption, we assessed the capacity of Bgn to modulate the action of fructose on brain and body. We exposed male biglycan knockout mice (Bgn 0/- ) to fructose for 7 weeks, and results showed that Bgn 0/- mice compensated for a decrement in learning and memory performance when exposed to fructose. These results were consistent with an attenuation of the action of fructose on hippocampal CREB levels. Fructose also reduced the levels of CREB and BDNF in primary hippocampal neuronal cultures. Bgn siRNA treatment abolished these effects of fructose on CREB and BDNF levels, in conjunction with a reduction in a fructose-related increase in Bgn protein. In addition, fructose consumption perturbed the systemic metabolism of glucose and lipids, that were also altered in the Bgn 0/ mice. Transcriptomic profiling of hypothalamus, hippocampus, and liver supported the regulatory action of Bgn on key molecular pathways involved in metabolism, immune response, and neuronal plasticity. Overall results underscore the tissue-specific role of the extracellular matrix in the regulation of metabolism and brain function, and support Bgn as a key modulator for the impact of fructose across body and brain., (Copyright © 2018. Published by Elsevier B.V.)

The complex neuropathology of traumatic brain injury (TBI) is difficult to dissect, given the convoluted cytoarchitecture of affected brain regions such as the hippocampus. Hippocampal dysfunction during TBI results in cognitive decline that may escalate to other neurological disorders, the molecular basis of which is hidden in the genomic programs of individual cells. Using the unbiased single cell sequencing method Drop-seq, we report that concussive TBI affects previously undefined cell populations, in addition to classical hippocampal cell types. TBI also impacts cell type-specific genes and pathways and alters gene co-expression across cell types, suggesting hidden pathogenic mechanisms and therapeutic target pathways. Modulating the thyroid hormone pathway as informed by the T4 transporter transthyretin Ttr mitigates TBI-associated genomic and behavioral abnormalities. Thus, single cell genomics provides unique information about how TBI impacts diverse hippocampal cell types, adding new insights into the pathogenic pathways amenable to therapeutics in TBI and related disorders.

A water resources index based on weight-accumulated precipitation over the passage of time in heavy rainfall events is used in this study for monitoring flood risk and peak danger, as well as to develop flood warnings. In this research, an hourly water resources index (WRI hr ) based on rainfall accumulations over the passage of time is proposed. WRI hr is able to monitor flood risk by taking into account the hourly effective precipitation that accumulates the precipitation (P hr ) of both current and antecedent hours, while the contributions from the preceding hours is subjected to a time-dependent reduction function that addresses the depletion of water volume by various hydrological processes (e.g., discharge, runoff, evapotranspiration). By converting rainfall into a water resources index (WRI), the hourly precipitation over a 24-h period is redistributed to formulate a long-term water resources index (WRI hr-L ) that monitors flood status based on long-term (more than 1 year) fluctuations in P hr and a short-term water resources index (WRI D-hr-S ) that considers shorter (D = 24-148 hourly) accumulations of the P hr data. WRI was assessed for its potential in flood monitoring at two hydrologically diverse sites: Dobong (South Korea; August 1998) and Brisbane (Australia; December 2010-January 2011), and its applicability was verified using river water level (H) measurements at hydrological stations. The power spectrum density and spectral coherence of hourly rainfall, river water level, and the corresponding WRI showed good agreements, as did the low and high frequency wavelet components using the discrete wavelet transform algorithm. Importantly, WRI 24-hr-S computed over 24 hourly accumulation periods was able to mimic the risk of short-term (flash-style) floods caused by concentrated rainfall, whereas WRI hr-L was more useful for flood risk assessment caused by an event over a long-term period. Dynamical changes in H were closely in-phase with the patterns of change noted in the WRI hr over the respective temporal scale. We conclude that the proposed WRI was able to replicate the flood evolution over the passage of time and, therefore, could possibly aid in the early warning of water-related disasters, demonstrating its practicality for continuous monitoring of the flood risk when a sustained period of rainfall event is observed.

Chronic fructose ingestion is linked to the global epidemic of metabolic syndrome (MetS), and poses a serious threat to brain function. We asked whether a short period (one week) of fructose ingestion potentially insufficient to establish peripheral metabolic disorder could impact brain function. We report that the fructose treatment had no effect on liver/body weight ratio, weight gain, glucose tolerance and insulin sensitivity, was sufficient to reduce several aspects of hippocampal plasticity. Fructose consumption reduced the levels of the neuronal nuclear protein NeuN, Myelin Basic Protein, and the axonal growth-associated protein 43, concomitant with a decline in hippocampal weight. A reduction in peroxisome proliferator-activated receptor gamma coactivator-1 alpha and Cytochrome c oxidase subunit II by fructose treatment is indicative of mitochondrial dysfunction. Furthermore, the GLUT5 fructose transporter was increased in the hippocampus after fructose ingestion suggesting that fructose may facilitate its own transport to brain. Fructose elevated levels of ketohexokinase in the liver but did not affect SIRT1 levels, suggesting that fructose is metabolized in the liver, without severely affecting liver function commensurable to an absence of metabolic syndrome condition. These results advocate that a short period of fructose can influence brain plasticity without a major peripheral metabolic dysfunction., (Copyright © 2017 Elsevier B.V. All rights reserved.)

While organo-inorganic halide perovskite solar cells show great potential to meet future energy needs, their thermal instability raises serious questions about their commercialization viability. At present, the stability of perovskite solar cells has been studied under various environmental conditions including humidity and temperature. Nonetheless, understanding of the performance of CH 3 NH 3 PbI 3-x Cl x perovskite solar cells is limited. This study reports the irreversible performance degradation of CH 3 NH 3 PbI 3-x Cl x perovskite solar cells during the heating and cooling processes under AM 1.5 and unveils what triggers the irreversible performance degradation of solar cells. Particularly, the primary cause of the irreversible performance degradation of CH 3 NH 3 PbI 3-x Cl x is quantitatively analyzed by monitoring in real time the development of deteriorated crystallinity, charge trapping/detrapping, trap depth, and the PbI 2 phase, namely a critical signal of perovskite degradation while varying the temperature of the perovskite films and solar cells. Most surprisingly, it is revealed that the degradation of both perovskite films and solar cells was triggered at ∼70 °C. Remarkably, even after the device temperature cooled down to room temperature, the degraded performance of the solar cells persisted with increasing charge trapping and further development of the PbI 2 phase. Identification of the irreversible performance degradation of perovskite solar cells provides guidance for future development of more stable perovskite solar cells.

For large-area, printable, and flexible electronic applications using advanced semiconductors, novel dielectric materials with excellent capacitance, insulating property, thermal stability, and mechanical flexibility need to be developed to achieve high-performance, ultralow-voltage operation of thin-film transistors (TFTs). In this work, we first report on the facile fabrication of multifunctional hybrid multilayer gate dielectrics with tunable surface energy via a low-temperature solution-process to produce ultralow-voltage organic and amorphous oxide TFTs. The hybrid multilayer dielectric materials are constructed by iteratively stacking bifunctional phosphonic acid-based self-assembled monolayers combined with ultrathin high-k oxide layers. The nanoscopic thickness-controllable hybrid dielectrics exhibit the superior capacitance (up to 970 nF/cm 2 ), insulating property (leakage current densities <10 -7 A/cm 2 ), and thermal stability (up to 300 °C) as well as smooth surfaces (root-mean-square roughness <0.35 nm). In addition, the surface energy of the hybrid multilayer dielectrics are easily changed by switching between mono- and bifunctional phosphonic acid-based self-assembled monolayers for compatible fabrication with both organic and amorphous oxide semiconductors. Consequently, the hybrid multilayer dielectrics integrated into TFTs reveal their excellent dielectric functions to achieve high-performance, ultralow-voltage operation (< ± 2 V) for both organic and amorphous oxide TFTs. Because of the easily tunable surface energy, the multifunctional hybrid multilayer dielectrics can also be adapted for various organic and inorganic semiconductors, and metal gates in other device configurations, thus allowing diverse advanced electronic applications including ultralow-power and large-area electronic devices.

Loss of pericytes, considered an early hallmark of diabetic retinopathy, is thought to involve abnormal activation of protein kinase C (PKC). We previously showed that the anti-amyotrophic lateral sclerosis (ALS) drug riluzole functions as a PKC inhibitor. Here, we examined the effects of riluzole on pathological changes in diabetic retinopathy. Pathological endpoints examined in vivo included the number of pericytes and integrity of retinal vessels in streptozotocin (STZ)-induced diabetic mice. In addition, PKC activation and the induction of monocyte chemotactic protein (MCP1) were assessed in diabetic mice and in human retinal pericytes exposed to advanced glycation end product (AGE) or modified low-density lipoprotein (mLDL). The diameter of retinal vessels and the number of pericytes were severely reduced, and the levels of MCP1 and PKC were increased in STZ-induced diabetic mice. Administration of riluzole reversed all of these changes. Furthermore, the increased expression of MCP1 in AGE- or mLDL-treated cultured retinal pericytes was inhibited by treatment with riluzole or the PKC inhibitor GF109203X. In silico modeling showed that riluzole fits well within the catalytic pocket of PKC. Taken together, our results demonstrate that riluzole attenuates both MCP1 induction and pericyte loss in diabetic retinopathy, likely through its direct inhibitory effect on PKC., (Copyright © 2016. Published by Elsevier Inc.)

Whereas aberrant brain connectivity is likely the core pathology of autism-spectrum disorder (ASD), studies do not agree as to whether hypo- or hyper-connectivity is the main underlying problem. Recent functional imaging studies have shown that, in most young ASD patients, cerebral cortical regions appear hyperconnected, and cortical thickness/brain size is increased. Collectively, these findings indicate that developing ASD brains may exist in an altered neurotrophic milieu. Consistently, some ASD patients, as well as some animal models of ASD, show increased levels of brain-derived neurotrophic factor (BDNF). However, how BDNF is upregulated in ASD is unknown. To address this question, we propose the novel hypothesis that a putative zinc-metalloprotease-BDNF (ZMB) axis in the forebrain plays a pivotal role in the development of hyperconnectivity and megalencephaly in ASD. We have previously demonstrated that extracellular zinc at micromolar concentrations can rapidly increase BDNF levels and phosphorylate the receptor tyrosine kinase TrkB via the activation of metalloproteases. The role of metalloproteases in ASD is still uncertain, but in fragile X syndrome, a monogenic disease with an autistic phenotype, the levels of MMP are increased. Early exposure to lipopolysaccharides (LPS) and other MMP activators such as organic mercurials also have been implicated in ASD pathogenesis. The resultant increases in BDNF levels at synapses, especially those involved in the zinc-containing, associative glutamatergic system may produce abnormal brain circuit development. Various genetic mutations that lead to ASD are also known to affect BDNF signaling: some down-regulate, and others up-regulate it. We hypothesize that, although both up- and down-regulation of BDNF may induce autism symptoms, only BDNF up-regulation is associated with the hyperconnectivity and large brain size observed in most young idiopathic ASD patients. To test this hypothesis, we propose to examine the ZMB axis in animal models of ASD. Synaptic zinc can be examined by fluorescence zinc staining. MMP activation can be measured by in situ zymography and Western blot analysis. Finally, regional levels of BDNF can be measured. Validating this hypothesis may shed light on the central pathogenic mechanism of ASD and aid in the identification of useful biomarkers and the development of preventive/therapeutic strategies.

Metallothionein-3 (Mt3), a zinc (Zn)-regulatory protein mainly expressed in the central nervous system, may contribute to oxidative cell death. In the present study, we examined the possible role of Mt3 in streptozotocin (STZ)-induced islet cell death and consequent hyperglycemia. Quantitative real-time polymerase chain reaction (RT-PCR) confirmed that islet cells expressed Mt3 mRNA. In all cases, wild-type (WT) mice injected with STZ exhibited hyperglycemia 7-21 days later. In stark contrast, all Mt3-null mice remained normoglycemic following STZ injection. STZ treatment increased free Zn levels in islet cells and induced their death in WT mice, but failed to do so in Mt3-null mice. Consistent with this, cultured Mt3-null islet cells exhibited striking resistance to STZ toxicity. Notably, PDE3a (phosphodiesterase 3A) was downregulated in islets of Mt3-null mice compared to those of WT mice, and was not induced by STZ treatment. Moreover, the PDE3 inhibitor cilostazol reduced islet cell death, likely by increasing cAMP levels, further supporting a role for PDE3 in STZ-induced islet cell death. Collectively, these results demonstrate that Mt3 may act through PDE3a to play a key role in Zn dyshomeostasis and cell death in STZ-treated islets.

In the brain, free zinc levels are under the exquisite control of a variety of zinc-regulating systems, in which zinc transporter (ZnT) proteins play a central role. ZnT3, which is prominently expressed in the brain, facilitates the concentration of free zinc in pre-synaptic vesicles. In addition to histochemical staining methods, a variety of zinc-specific fluorescence dyes has been developed to image or analyze zinc in brain tissue. In this study, we demonstrate the close correlations between histofluorescently reactive zinc and ZnT3. We examined the overlapping distribution of the zinc-specific fluorescent dye, N-(6-methoxy-8-quinolyl)-p-toluenesulfonamide (TSQ)-, and ZnT3-immunoreactive fluorescence throughout the normal brain. TSQ and ZnT3-antibody intensely stained the hippocampus, cortex and amygdala, highlighting the characteristic laminar organization of these regions by variably staining the different layers. TSQ fluorescence and ZnT3 immunoreactivity were roughly co-localized with synaptophysin along the neuropil, but were absent in the neuronal soma. However, albeit relatively faint, TSQ fluorescence was also found throughout the brains of ZnT3-knockout mice. Although these results may indicate the presence of very small cerebral free zinc pools distinct from synaptic vesicle zinc, the synaptic vesicle zinc pool is predominant, accounting for more than 95% of the entire histofluorescently reactive zinc pool in the hippocampus and cortex. Thus, the physiological activity of free zinc in the normal brain might largely depend on the pool of synaptic vesicle zinc that is determined by ZnT3., (Copyright © 2011 Elsevier B.V. All rights reserved.)

In the present study, we examined whether metallothionein-3 (Mt3), a zinc-binding protein that is specifically enriched in a brain, plays a role in obesity and hypothalamic leptin signaling in mice. Upon aging, male Mt3-null mice gained more body weight than male wild-type mice; however, the daily amount of food intake was little different. Rather, the obesity in male Mt3-null mice was likely the result of decreased metabolic rates, as indicated by lower oxygen consumption and carbon dioxide production. Consistent with this, mRNA levels for the mitochondrial proton carrier UCP1 were reduced in brown adipose tissue of Mt3-null mice. Although Mt3-null mice showed increases in serum leptin levels, probably due to increased fat mass, the level of the leptin receptor (Lepr) in the hypothalamus of these mice was significantly reduced. In addition, levels of phosphorylated extracellular signal-regulated kinase (p-Erk-1/2) were also reduced in the hypothalamus of Mt3-null mice. Because zinc released from Mt3 may activate Erk-1/2, we examined whether zinc is involved in the upregulation of Lepr levels through the activation of Erk-1/2. Consistent with this possibility, exposure of hypothalamic cells to zinc activated Erk-1/2 and induced Lepr expression in an Erk-dependent manner. The present results demonstrate that Mt3 in the brain of male mice, particularly in the hypothalamus, may be involved in central leptin signaling and the consequent increase in peripheral energy expenditure. In addition to providing insight into the role of zinc and metallothioneins in the development of obesity, this new information may help design ways to overcome the pervasive problem of obesity., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Recent studies have demonstrated that clioquinol, an antibiotic with an anti-amyloid effect, acts as a zinc ionophore under physiological conditions. Because increases in labile zinc may induce autophagy, we examined whether clioquinol induces autophagy in cultured astrocytes in a zinc-dependent manner. Within 1h of exposure to 0.1-10 μM clioquinol, the levels of microtubule-associated protein 1 light chain 3 (LC3)-II, a marker of autophagy, began to increase in astrocytes. Confocal live-cell imaging of GFP-LC3-transfected astrocytes showed the formation of LC3(+) autophagic vacuoles (AVs), providing a further indication that clioquinol induced autophagy. Addition of 3-methyladenine or small-interfering RNA against autophagy-related gene 6 (ATG6/Beclin-1) blocked clioquinol-induced increases in LC3-II. FluoZin-3 fluorescence microscopy showed that, like the zinc ionophore pyrithione, clioquinol increased intracellular zinc levels in the cytosol and AVs in an extracellular zinc-dependent manner. Zinc chelation with N,N,N',N'-tetrakis-(2-pyridylmethyl) ethylenediamine (TPEN) reduced, and addition of zinc increased the levels of LC3-II and LC3(+) puncta, indicating that zinc influx plays a key role therein. Moreover, astrocytes and SH-SY5Y cells expressing mutant huntingtin (mHttQ74) accumulated less aggregates when treated with clioquinol, and this effect was reversed by TPEN. These results indicate that clioquinol-induced autophagy is likely to be physiologically functional. The present study demonstrates that clioquinol induces autophagy in a zinc-dependent manner and contributes to clearance of aggregated proteins in astrocytes and neurons. Hence, in addition to its metal-chelating effect in and around amyloid beta (Aβ) plaques, clioquinol may contribute to the reduction of Aβ loads by activating autophagy by increasing or normalizing intracellular zinc levels in brain cells., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Although the majority of epileptic seizures can be effectively controlled with antiepileptic drugs and/or surgery, a significant number progress to status epilepticus of sufficient duration to cause permanent brain damage. Combined treatment with antiepileptic drugs and neuroprotective agents, however, may help protect these individuals from permanent brain damage. Since toxicity induced by endogenous zinc contributes to epileptic brain injury, and since pyruvate is effective in reducing zinc-triggered neuronal death in cortical culture as well as ischemic neuronal death in vivo, we examined whether systemic pyruvate administration reduces seizure-induced brain damage. Na pyruvate (500 mg/kg) or osmolarity-matched saline (265 mg/kg NaCl, i.p.) were given to adult SD rats 30 or 150 min after 10 mg/kg kainite injection (i.p.), and there was no significant difference in the time course or severity of seizures between these groups. Zinc accumulation in neuronal cell bodies in the hippocampus, however, was much lower in the pyruvate than in the saline group. There was a close correlation between zinc accumulation and cell death, as assessed by acid-fuchsin and TUNEL staining. Pyruvate treatment markedly reduced neuronal death in the hippocampus, neocortex and thalamus. Pyruvate increased HSP-70 expression in hippocampal neurons. These results suggest that pyruvate, a natural glucose metabolite, may be useful as adjunct treatment in status epilepticus to reduce permanent brain damage.

Although the tissue plasminogen activator (tPA)/plasminogen/plasmin proteolytic system is thought to modulate the catabolism of amyloid-beta (Abeta), in vivo evidence remains insufficient. In the brain of human amyloid precursor protein transgenic Tg2576 mice, we found co-accumulation of tPA and plasminogen at the periphery of compact amyloid deposits, mainly Abeta42-cored plaques, as well as in the walls of blood vessels with cerebral amyloid angiopathy (CAA). This tPA/plasminogen system contained high levels of proteolytic activity. High levels of tPA were also found in reactive astrocytes with increased Abeta42 expression, whereas plasminogen was found only in neurons. When the brain sections of Tg2576 mice were treated with both tPA and plasminogen, levels of thioflavin-S fluorescence, congophilicity and birefringence in the compact amyloid plaques were significantly reduced, and the ultrastructure of Abeta42-fibrils was disrupted. These results suggest that the assembled Abeta42 may promote upregulation of the tPA/plasminogen proteolytic system, which can modulate the deposition of amyloid plaques in vivo.

An autopsy case of disseminated HSV type 2 infection occurring in a neonate at 32 weeks' gestation, delivered by cesarean section after premature rupture of membrane of 7 days duration, is presented. Herpes simplex virus type 2 was isolated from the vesicular skin lesion. The mother and patient had specific antibody to type 2 herpes simplex virus. Patient's parents had denied any herpetic orolabial or genital lesion during or before this pregnancy. Cultures from the cervical and vaginal swabs of the mother were negative for HSV. Postmortem examination showed hepatic necrosis, skin vesicle, devastating necrotizing inflammation of the brain, chorioretinitis and interstitial pneumonitis.